Antimicrobial wounddressing

ABSTRACT

An antimicrobial composite which comprises a first, liquid-permeable layer and a second layer arranged on the first layer. An antimicrobial metal in elemental form is present between the first and second layers and substantially no antimicrobial metal in elemental form is present on exterior surfaces of the composite. This abstract is neither intended to define the invention disclosed in this specification nor intended to limit the scope of the invention in any way.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.10/654,949, filed Sep. 5, 2003 and is a continuation of InternationalApplication No. PCT/EP2004/006213, filed Jun. 9, 2004, the entiredisclosure whereof is expressly incorporated by reference herein, whichis a continuation of U.S. application Ser. No. 10/654,949, filed Sep. 5,2003, and claims priority of German Patent Application No. 103 28 261.0,filed Jun. 23, 2003, the entire disclosure whereof is expresslyincorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to antimicrobial composites which may beused, in particular, as wound coverings, dressings, cloths, and thelike. By coating one side of a liquid-permeable material with anantimicrobial metal such as silver and laminating the resultant materialto a material such as a liquid-absorbing nonwoven material with themetal coating facing the liquid-absorbing material, the abrasion ofmetal particles may be prevented while at the same time, theantimicrobial and disinfectant effect of the metal coating is retained.

B 2. Discussion of Background Information

Treating and healing bacterially contaminated skin and wounds, orinfected skin and wounds is a major challenge to medicine and thenatural sciences. Poorly healing and chronic wounds frequently becomepopulated by a wide variety of microorganisms that considerably delayhealing and sometimes even prevent healing altogether. Frequently, inthe case of acute wounds that are caused by trauma, surgicalintervention or even just simple injury, the penetration and infectionby pathogenic microorganisms can, however, not completely be prevented.

Various possibilities are described for removing microorganisms from thecontaminated or infected tissue of a wound and/or for killing themicroorganisms. In addition to the oral administration of antibiotics,the removal of pathogenic microorganisms from a wound may be achieved,in accordance with the prior art, by the topical application of adisinfectant or an antibiotic. However, antiseptics and antibiotics arecytotoxic; in addition, many pathogenic strains have developedresistances to antibiotics.

An example of the known antimicrobial and/or prophylactic treatment ofcontaminated or infected wounds is the use of oxidants such as tinctureof iodine, or of antiseptics such as ointments which contain silversulfadiazine.

For a very long time, silver has been the agent of choice for treatinginfections, due to its broad bactericidal and fungicidal effect. Inaddition to its broad range of activity, silver is effective in minute,i.e., trace amounts (oligodynamic effect). Since the amounts of silverare so small, the tolerance is excellent. For example, silver aerosols,silver-containing solutions, ointments or tablets, etc. are widely usedas antiseptics.

Silver-containing products are also used in the form of correspondingantimicrobially treated or impregnated wound dressings and wound carematerials. The use of silver-containing zeolites, glasses and zirconylphosphates, and also of silver in elemental or nanocrystalline form, isknown as well.

Basically, there are two forms used for the administration of silver(ions), i.e., forms in which the silver ions are present in the productper se, and forms in which the ionic form of silver is generated by theoxidation of elemental silver. The first case essentially involves adissolution or ion-exchange process. This makes the silver ions rapidlyavailable, but the amount of silver ions in the preparation dropsquickly as well. To provide a sufficient amount of silver to counteractthis disadvantage is not without problems. For example, the cytotoxicityof silver ions limits the maximum acceptable amount thereof that can beused in a product.

Another disadvantage is that silver is deactivated by proteins, othercomplex-formers, or in the presence of ions that form scarcely-solublesilver salts. These conditions doubtlessly exist in wound fluids. Incontrast, the release of silver from “elemental” silver (silver metal)is slower and occurs over a longer period, but takes place continuously.Accordingly, a sufficient amount of silver ions that is harmless to theuser can always be released from the reservoir of elemental silver, theamount of silver ions depending on whether more or less of these ionscan be released by equilibrium processes. The release of silver is,therefore, “as needed,” and the release of an effective quantity ofsilver is ensured.

An overview of known antimicrobial, silver-containing wound carematerials is given in DE-A1-19958458.

A commercially available wound care product with antimicrobialproperties is known under the name of Arglaes®. Its mode of action isbased on “slow-release polymer” technology that causes a slow butconstant release of silver ions in the moist milieu of the wound(Biomed. Mat., November 1995; Health Industry Today, 1 Nov. 1997, Vol.58, No. 11).

DE-A1-19958458 discloses wound coverings comprising a synthetic polymermaterial which contains metal ion-containing zeolites.

Silver-containing glasses that have an antimicrobial effect are knownfrom EP-A1-1116698 and EP-A1-1116700. These glasses are embedded inthermoplastic polymers that are used in a wide variety of forms forhousehold and hygienic applications such as wallpaper, cutting boards,etc.

U.S. Pat. No. 5,753,251 and 5,681,575 describe antimicrobial coatingswith so-called nanocrystalline silver that are formed on a medicalproduct by depositing metals such as, e.g., silver from a gas phase. Theantimicrobial effect is based on the release of ions, atoms, moleculesor clusters from a disordered metal lattice when the silver is incontact with water or alcohol-based electrolytes. The correspondingproduct is known under the name Acticoat®. One of the disadvantages ofthis product is the visibly identifiable silver abrasion that causes ablack discoloration of the covered skin area.

U.S. Pat. No. 2,934,066 describes a wound covering coated with metals,especially silver, which is reported to have a disinfecting effect.

The entire disclosures of the documents cited above, as well as those ofall other documents mentioned in the present specification, areexpressly incorporated by reference herein as if each of these documentsin its entirety were part of the present specification.

Wound coverings comprising a non-woven material that is covered with asilver-coated polyethylene mesh are also known, e.g., Katomed®.

In all of the known disinfectant wound dressings which comprise acoating of elemental or nanocrystalline silver, the silver coating isintended to directly contact the wound. A disadvantage of thesedisinfecting materials is, therefore, that upon their contacting of theskin or wound they give rise to an abrasion and release of smallparticles of elemental silver. These particles form inclusions in theskin or wound, so-called granulomas, and can lead to complicationsduring wound healing. Furthermore, due to the generated blackdiscoloration, the aesthetic acceptance of corresponding products amongusers is very low.

It would be desirable to have available a material, e.g., a skin orwound dressing, which does not show the disadvantages of the knownmaterials, but nevertheless shows antimicrobial activity.

SUMMARY OF THE INVENTION

The present invention provides an antimicrobial composite comprising afirst, liquid-permeable layer and a second layer arranged on the firstlayer. An antimicrobial metal in elemental form is present between theselayers. Moreover, substantially none of this antimicrobial metal inelemental form is present on exterior surfaces of the composite.

In one aspect of the composite, the first layer may comprise aforamenous structure, and preferably comprises a hole structure and/or amesh structure. For example, the first layer may comprise a perforatedfilm and/or a mesh.

In another aspect of the composite, the first layer may comprise anorganic polymer, preferably, a polyolefin such as, e.g., polyethyleneand/or polypropylene

In yet another aspect, the first layer may comprise a polyethylene mesh.

In a still further aspect, the first layer preferably comprises openingshaving a size of from about 250 μm to about 1400 μm, e.g., from about400 μm to about 700 μm. In one embodiment, the openings may have asubstantially triangular shape and/or may provide an open area of fromabout 15% to about 60% of the surface area of the first layer.

In another aspect of the composite, the first layer may have a thicknessof from about 0.02 mm to about 0.8 mm, e.g., of from about 0.05 mm toabout 0.5 mm.

In a still further aspect, the second layer is a liquid-permeable layeror a liquid-absorbing layer.

In another aspect, the second layer may comprise a perforated filmand/or a mesh.

In yet another aspect, the second layer may comprise an organic polymer.The organic polymer may comprise a polyolefin. For example, the secondlayer may comprise a polyethylene mesh.

In a still further aspect of the composite of the present invention, thesecond layer preferably has a thickness of from about 0.02 mm to about2.5 mm.

In another aspect, the second layer may be a liquid-absorbing layer.This layer may have a liquid-absorbing capacity of from about 300 g/m²to about 2000 g/m², e.g., from about 400 g/m² to about 1000 g/m². Forexample, the liquid-absorbing layer may comprise a textile sheet, whichtextile sheet may in turn comprise a nonwoven, a fleece, a woven fabric,a knit and/or a felt.

In a still further aspect, the second layer may comprise fibers and/oryarns.

In another aspect, the second layer may comprises viscose, polyolefin(e.g., polyethylene and/or polypropylene) and/or polyester.

In another aspect of the composite, the second layer preferably has athickness of from about 0.3 mm to about 2.4 mm, e.g., from about 0.5 mmto about 1.4 mm and/or an area weight of from about 80 g/m² to about 200g/m².

In a still further aspect, the second layer may comprise asuperabsorber, for example, a superabsorber comprising a polymer havingrecurring units derived from acrylic acid and derivatives thereof.. Thesuperabsorber may be present in an amount of from about 0.01% to about40% by weight, based on the weight of the second layer.

In another aspect of the composite of the present invention, theantimicrobial metal preferably comprises at least one of Ag, Au, Pd, Pt,Cu, Ir, Zn, Sn, Sb, Bi and/or an alloy comprising one or more of thesemetals. Preferably, the antimicrobial metal comprises Ag and/or an alloythereof.

In yet another aspect of the present composite, the antimicrobial metalmay be provided as a coating on at least one of the surfaces of thefirst and second layers.

In another aspect of the composite, the antimicrobial metal may bepresent as a layer which comprises the antimicrobial metal and isarranged between the first and second layers.

In a still further aspect, the composite preferably has a sheet-like(web-like) structure.

In yet another aspect of the composite of the present invention, theantimicrobial metal (e.g., silver) preferably is present in an amount offrom about 1 mg/m² to about 1 g/m² of composite, e.g., in an amount offrom about 10 mg/m² to about 600 mg/m² of composite, more preferably inan amount of from about 50 mg/m² to about 450 mg/m² of composite, e.g.,in an amount of from about 60 mg/m² to about 80 mg/m² of the composite.

In another aspect of the composite of the present invention, the firstlayer has a silver coating on the side (surface) thereof which faces thesecond layer and/or the second layer has a silver coating on the side(surface) thereof which faces the first layer. In yet another aspect, anintermediate layer is arranged between the silver coating and the firstlayer. The intermediate layer preferably comprises aluminum.

In yet another aspect of the composite, the composite preferably has anarea weight of from about 50 g/m² to about 300 g/m², e.g., from about 80g/m² to about 160 g/m², and/or a thickness of from about 0.4 mm to about2.5 mm, e.g., from about 0.5 mm to about 1.4 mm, and/or a peelingstrength of from about 0.05 N/cm to about 1.5 N/cm, e.g., from about0.15 N/cm to about 0.8 N/cm, and/or a maximum tensile strength of fromabout 10 N/cm to about 40 N/cm, and/or a 24-hour release of theantimicrobial metal (e.g., silver) of from about 0.05 mg/m² to about 3mg/m² of composite, e.g., of from about 0.1 mg/m² to about 2 mg/m² ofcomposite and/or a size of at least about 0.5 cm² and/or a size of nothigher than about 1 m².

The present invention also provides a wound covering article, a skincare article and a diaper, all of which comprise the above composite,including all of the various aspects thereof.

The wound covering article, for example, may further comprise a backingmaterial arranged on the second layer of the composite. The backingmaterial may carry an adhesive, e.g., a UV-curable acrylic adhesive or arubber-based hot melt adhesive, on the side thereof which faces thesecond layer. Furthermore, the backing material preferably comprises apolyester nonwoven and/or a polyethylene film.

The present invention also provides a method of covering a wound. Themethod comprises placing the above wound covering article, including thevarious aspects thereof, on the wound so that the first layer of thecomposite contacts the wound.

The present invention also provides a method of covering a wound. Themethod comprises providing a material which comprises a liquid-permeablelayer and an antimicrobial metal in elemental form associated with thislayer (e.g., coated with the metal and/or having the metal incorporatedtherein and/or being in (direct) contact with the metal, etc.), andplacing the material on the wound so that a surface of theliquid-permeable layer which is substantially free of the antimicrobialmetal in elemental form contacts the wound.

In one aspect of the method, the liquid-permeable layer preferablycomprises a foramenous material, e.g., a hole and/or a mesh structure.For example, the liquid-permeable layer may comprise a perforated filmand/or a mesh, e.g., a polyolefin mesh.

The present invention also provides a process of making an antimicrobialcomposite as set forth above. The process comprises bonding together afirst, liquid-permeable material and a second material which isliquid-permeable and/or liquid-absorbing. At least one of the first andsecond materials is coated with an antimicrobial metal in elemental formon a side (surface) thereof which faces the other material, whereassubstantially no antimicrobial metal in elemental form is present on theexterior surface of the composite.

In one aspect, the process may comprise providing a liquid-permeable,sheet-like material, coating one side of the material with theantimicrobial metal and bonding a liquid-absorbing material to that sideof the liquid-permeable material which has the antimicrobial metalthereon. The liquid-permeable material preferably comprises a holeand/or a mesh structure. In another aspect of the process, theliquid-permeable material may be coated with the metal by a techniquewhich comprises vapor deposition, e.g., by vacuum evaporation,sputtering, ion-beam assisted deposition, ion plating or magnetronsputtering.

In another aspect of the process of the present invention, theliquid-permeable material has an intermediate coating on that sidethereof which is to be coated with the antimicrobial metal. Theintermediate coating preferably comprises aluminum in metallic form.

In a still further aspect of the present process, the liquid-absorbingmaterial and the liquid-permeable material are bonded to each other bylamination under heat and/or pressure, gluing, welding, and/or sewing.

As mentioned above, the first layer of the composite of the presentinvention is a liquid-permeable layer. The term “liquid-permeable” asused in the present specification and the appended claims isinterchangeable with the term “fluid-permeable” and denotes a materialwhich is capable of allowing liquid (fluid) such as water, woundsecretions (wound exudate) etc., present on one side of the material toget to the opposite side of the material, irrespective of the way and/ormechanism through which this is accomplished. Accordingly, any materialwhich is not completely impervious to liquid (fluid) is“liquid-permeable” for the purposes of the present invention. In thisregard, it should be noted that a liquid-absorbing material may becomeliquid-permeable once the liquid absorbing capacity of the material isexceeded. Preferably, the liquid-permeable material has a foramenousstructure, e.g., a hole or mesh structure. Non-limiting examples ofcorresponding materials are a perforated film and a mesh.

The material of the first layer will usually comprise one or moresubstantially bioinert materials, e.g., a (natural, semisynthetic orsynthetic) organic polymer, preferably, a polyolefin such as, e.g.,polyethylene and/or polypropylene. However, materials different fromorganic polymers may be used as well, as long as they can be made tobe—or already are—liquid-permeable. If the composite of the presentinvention is to be used in wound-care applications, the material ispreferably substantially non-adhering to the wound.

Particularly in cases where the liquid-permeable material comprises anet, the openings thereof preferably have an (average) size (=length ofthe longest bisector) of at least about 250 μm, e.g., at least about 400μm, and not higher than to about 1400 μm, e.g., not higher than about1000 μm, or not higher than about 700 μm. The openings may be of anyshape such as, e.g., circular, triangular, rectangular, etc., anddifferent shapes and/or different sizes of openings may be present inthe same material. Preferably, the open area created by these openingsis at least about 15%, e.g., at least about 25%, and not more than about60%, e.g., not more than about 50%, of the surface area of the firstlayer. The same applies to other liquid-permeable structures such as,e.g., perforated films, although in this case the size of the holeopenings may be by far larger than those usually encountered with a netstructure (e.g., up to about 3 mm or even larger). Holes may be created(e.g., in a film) by many different techiques, e.g., by mechanicalperforation, punching, embossing, flame-perforation, etc. Moreover,holes may be present in the material from the beginning, e.g., in thecase of nonwovens (e.g., spun bonded nonwovens), and woven or knittedfabrics.

The first layer will usually have a thickness of at least about 0.02 mm,e.g., at least about 0.05 mm, or at least about 0.1 mm. Usually thethickness of the first layer will be not higher than about 0.8 mm, e.g.,not higher than about 0.5 mm, or not higher than about 0.3 mm. It shouldbe noted that while it is currently preferred for the first layer to becomposed of a single layer, the first layer of the composite of thepresent invention may itself be a composite of two or more individuallayers (e.g., a combination of a perforated film and a mesh), in whichcase the above thickness values refer to the entire first layer. Theunit area weight of the first layer, including any antimicrobial metalwhich may be combined therewith (in particular, silver), preferably isin the range of from about 10 g/m² to about 40 g/m², e.g., about 25 g/m²(as determined by DIN EN 29073-1).

It should also be noted that the first layer of the composite of thepresent invention may have a variety of substances on the surfacethereof which is to contact the wound, provided these substances do notinterfere to any significant extent with the liquid-permeability of thelayer and the antimicrobial effect exerted by the metal. Non-limitingexamples of such substances are compounds and compositions which promotewound healing and/or have a skin care effect.

Non-limiting examples of preferred materials for use in or as the firstlayer of the composite of the present invention are polyethylene netsavailable under the trade name Delnet® (Applied Extrusion Technologies,Wilmington, Del.). These nets are produced by extrusion, embossing andstretching of films. A huge variety of these nets is commerciallyavailable and may be produced by altering the polymer blend, the melttemperature, the embossing pattern, and the stretch ratio.

The second layer of the composite of the present invention will usuallybe liquid-absorbing, or at least liquid-permeable. Where thesecond-layer is (merely) liquid-permeable, the second layer may be thesame as, or similar to the first layer, and in this case the abovecomments with respect to the first layer may be referred to with respectto properties, structure, etc. of the second layer.

The second layer of the composite of the present invention preferably isa liquid-absorbing layer. The term “liquid-absorbing” as used in thepresent specification and in the appended claims denotes a materialwhich is capable of not only taking up a certain amount of liquid(fluid), but also of retaining the liquid within its structure underatmospheric pressure. Usually, a liquid-absorbing material will becapable of retaining an amount of liquid which equals at least about 5%,preferably at least about 10% of its own weight.

The liquid-absorbing capacity of the preferred liquid-absorbing secondlayer of the composite of the present invention (determined according toDIN 53923) will usually be at least about 300 g/m², e.g., at least about400 g/m², or at least about 500 g/m², but will usually not be higherthan about 2000 g/m², e.g., not higher than about 1500 g/m², not higherthan about 1000 g/m², or not higher than about 800 g/m². However, higherliquid-absorbing capacities than those given above may be moreappropriate in certain cases, for example, for compresses for use withlarger wounds.

Where the second layer is liquid-absorbing, the second layer may becomposed of any material that is liquid-absorbing and is compatible withthe intended use of the composite. Preferably, the liquid-absorbingmaterial will be substantially bioinert. For example, the second layermay comprise a textile sheet and/or a foam, e.g., a polyurethane foam.The textile sheet may comprise, by way of non-limiting example, anonwoven, a fleece, a woven fabric, a knit and/or a felt. Preferredexamples of the liquid-absorbing material include nonwovens, e.g.,nonwovens which are bonded by various technologies such as, e.g.,thermal bonding, stitch-bonding (Malivlies, Maliwatt), carding,spun-lacing, melt blowing, etc.

By way of non-limiting example, the second layer may comprise one ormore natural, semisynthetic and/or synthetic materials such as, e.g.,viscose, cellulose and derivatives thereof, polyolefins (e.g.,polyethylene and/or polypropylene), polyesters, polyetheresters,polyamides, polyurethanes, hydrocolloids, hydrogels, and in general,materials which are conventionally used for making woundcoverings/dressings.

The second layer of the composite of the present invention preferablyhas a thickness of at least about 0.3 mm, e.g., at least about 0.4 mm,or at least about 0.5 mm. The thickness will usually be not higher thanabout 2.4 mm, e.g., not higher than about 2.0 mm, or not higher thanabout 1.4 mm. Like in the case of the first layer, the second layer ofthe composite of the present invention may itself be a composite of twoor more individual layers (by way of non-limiting example, a combinationof two layers or sheets of different liquid-absorbing materials such as,e.g, a foam and a textile sheet), in which case the above values (andthose given below) refer to the entire second layer.

The desirable area weight of the second layer of the composite of thepresent invention depends on the intended use and the type oflamination. For standard bandage products for treating conventionalwounds the area weight of the second, liquid-absorbing layer (e.g., thenonwoven), as determined according to DIN EN 29073, will usually be notlower than about about 80 g/m², e.g., not lower than about 100 g/m², andbe not higher than about 200 g/m², e.g., not higher than about 150 g/m²,or not higher than about 130 g/m². An area weight of about 125 g/m² isparticularly preferred. In certain cases higher area weights than thoseindicated above may be more appropriate, for example, for compresses foruse with larger wounds.

Additionally, the second (liquid-absorbing) layer may comprise one ormore superabsorbers such as, for example, water-insoluble, cross-linkedpolymers that can swell and form hydrogels to absorb and store largeamounts of liquid (e.g., water), even under pressure. A non-limitingexample of a suitable superabsorber is a polymer which comprisesrecurring units derived from acrylic acid and derivatives thereof. Whenpresent at all, the superabsorber(s) will usually be present in anamount of from about 0.01% to about 40% by weight, based on the weightof the second layer.

The composite of the present invention comprises one or moreantimicrobial metals such as, e.g., Ag, Au, Pd, Pt, Cu, Ir, Zn, Sn, Sb,Bi, and alloys comprising one or more of these metals. A particularlypreferred metal is silver. The term “antimicrobial” as used in thepresent specification and the appended claims is to be understood in itsbroadest sense, and is inclusive of terms like “disinfectant”,“antibacterial”, “antifungal” etc. In particular, “antimicrobial”denotes activity against pathogenic microorganisms of any kind.

The antimicrobial metal in elemental form may be present between thefirst and second layers of the composite of the present invention in anyform which ensures that metal (ions) will be present on the externalsurface of the first layer (opposite the surface that faces the secondlayer) when this surface is contacted with (aqueous) liquid (water,liquid electrolyte, wound exudate etc.) for a sufficient period of time.Accordingly, the expression “present between the first and secondlayers” as used in the present specification and the appended claimsdoes not exclude, but rather includes, composites in which theantimicrobial metal is present within the first layer and/or within thesecond layer instead of, or in addition to, its presence between thelayers. By way of non-limiting example, the first layer of the compositeof the present invention may be composed of a combination of twoindividual liquid-permeable layers (e.g., a mesh and a perforated filmor two perforated films), and the antimicrobial metal may be sandwichedbetween (e.g., be present at the interface of) these two individuallayers. Thus, the present invention encompasses any composite whereinthe antimicrobial metal in elemental form is present within thecomposite, but substantially no antimicrobial metal in elemental form ispresent on exterior surfaces of the composite. “Substantially noantimicrobial metal in elemental form is present on exterior surfaces ofthe composite” means that no more than trace amounts of antimicrobialmetal, in particular, amounts which by themselves will not give rise toa noticeable antimicrobial effect, are present on exterior surfaces ofthe composite.

In a preferred embodiment of the composite of the present invention, theantimicrobial metal is present as a coating on at least one of thesurfaces of the first and second layers, preferably (at least) on one ofthe surfaces of the first layer, although a corresponding coating or thelike may also be present on one or both sides of the second layer.

The antimicrobial metal may be present as such (i.e., without any othermaterials), but it may also be present in any other suitable form, forexample, as a layer which comprises the antimicrobial metal and othermaterials such as, e.g., in the form of a porous polymer matrix whichcontains embedded antimicrobial metal.

The antimicrobial metal (e.g., silver) will usually be present in anamount of at least about 1 mg/m², e.g., at least about 10 mg/m², atleast about 50 mg/m², at least about 60 mg/m², or at least about 70mg/m². Usually the amount of silver will not be higher than about 1g/m², e.g., not higher about 600 mg/m², not higher than about 450 mg/m²,not higher than about 200 mg/m², or not higher than about 80 mg/m² ofthe composite.

One or more other layers may be arranged between the antimicrobial metaland the first layer and/or the second layer. For example, anintermediate layer may be arranged on the surface of the first layer(and/or the second layer) onto which the antimicrobial metal is to beapplied. The intermediate layer may serve various purposes, e.g., toprovide a higher optical density in order to improve the aestheticappearance (in particular, where the amount of antimicrobial metal isrelatively low) and/or to produce a more uniform coating and/or topromote adhesion of the antimicrobial metal, etc. The intermediate layerpreferably comprises aluminum (e.g., in the form of a thin aluminummetal film produced by deposition from the gas phase), but any othermaterial(s) can be used as well as long as they are suitable for thedesired purpose(s) and, in particular, do not interfere with the releaseof the antimicrobial metal and the antimicrobial activity thereof.

In a preferred embodiment of the composite of the present invention, thefirst layer of the composite is laminated to the second layer(preferably a liquid-absorbing layer such as, e.g., a nonwoven) by usingmeltable fibers under heat and pressure. Welding (e.g., ultrasonicwelding) is an example of the various other techniques which may beemployed for this purpose. In the case of spot-welding the bond betweenthe first layer, e.g., a mesh, and the second layer, e.g., aliquid-absorbing nonwoven, tends to be relatively weak, wherefore a typeof bonding with a larger contact area between these layers is preferred.Yet another non-limiting example of the techniques for bonding the firstand second layers together is the use of adhesives. In this case, theutilized adhesive should not significantly interfere with the release ofthe antimicrobial metal (e.g., silver) or cause inconvenience to theuser.

Preferably, the first layer of the composite of the present invention isbonded to the second layer by continuous bonding, e.g., substantiallycompletely (as opposed to bonding in certain places only, like in thecase of, e.g., spot-welding). Where the first layer is laminated to thesecond layer by using meltable fibers, a sufficient amount of meltablefibers should be used to ensure sufficient resistance againstdelamination.

The composite of the present invention (without any additional layerswhich may optionally be present, such as, e.g., a backing layer etc.)will preferably have an area weight (as determined according to DIN EN29073-1) of at least about 50 g/m², e.g., at least about 80 g/m², andnot more than about 300 g/m², e.g., not more than about 230 g/m², or notmore than about 160 g/m². Also, the composite preferably has a thickness(as determined according to DIN EN 29073-2) which is not lower thanabout 0.4 mm, e.g., not lower than about 0.5 mm, and not higher thanabout 2.5 mm, e.g., not higher than about 1.4 mm. Furthermore, thecomposite will usually show a peeling or delamination strength (asdetermined according to DIN 53357) of at least about 0.05 N/cm, e.g., atleast about 0.15 N/cm, and not higher than about 1.5 N/cm, e.g., nothigher than about 0.8 N/cm. The minimum single value of the peelingstrength (as determined according to DIN 053357) will usually not belower than 0.05 N/cm. Additionally, the composite will usually show amaximum tensile strength (as determined according to DIN EN 29073-3) offrom about 10 N/cm to about 40 N/cm. Furthermore, the 24-hour release ofantimicrobial metal (e.g., silver) provided by the composite of thepresent invention (as determined according to the method describedhereinbelow) preferably is at least about 0.05 mg/m², particularly, atleast about 0.1 mg/m², but usually it will not be higher than about 3mg/m², e.g., not higher than about 2 mg/m² of composite.

A wound covering article according to the present invention may, by wayof non-limiting example, comprise the above composite and a cover orbacking layer arranged on the second layer of the composite (e.g.,directly bonded to the second layer or to any intermediate layer suchas, e.g., a liquid-permeable layer which may optionally be present in acomposite wherein the second layer is made of a liquid-absorbingmaterial). The cover layer may comprise any material that is suitablefor this purpose. Non-limiting examples of corresponding materialsinclude a nonwoven (e.g., composed of polyester), a polyolefin (e.g.polyethylene) film and a combination thereof. The cover layer may carryan adhesive on the surface which is to come into contact with the second(or intermediate) layer and, optionally, also with the skin.Non-limiting examples of suitable adhesives are disclosed in, e.g., DE27 43 979 C3. For example, commercially available pressure-sensitive orUV-curable adhesives based on acrylate or rubber may be used for thispurpose. Preferable is the use of thermoplastic hot-melt adhesives basedon natural and synthetic rubbers and other synthetic polymers such as,e.g., acrylates, methacrylates, polyurethanes, polyolefins, polyvinylderivatives, polyesters and silicones. These adhesives may optionallycontain additives such as, e.g., tackifying resins, softeners,stabilizers and other auxiliary agents. Subsequent cross-linking of theadhesive by UV or electron beam radiation may be advantageous.

Hot-melt adhesives based on block copolymers, in particular, aredistinguished by their numerous varieties. By specifically lowering theglass transition temperature of the pressure-sensitive adhesive throughselection of the appropriate tackifier, softener, the polymer moleculesize and molecular weight distribution of the individual components, anappropriate adhesion to the skin is ensured also at critical locationsof the human locomotive system.

It has surprisingly been found that, for example, a wound coveringarticle which does not have the antimicrobial metal (e.g., silver) onthe surface of a liquid-permeable layer which is to come into contactwith the wound (i.e., not on an external surface thereof), but has themetal on the opposite surface of the layer, is capable of releasing asufficient amount of the metal to give rise to an antimicrobial(disinfectant) effect when the article is in contact with a wound.

It is surprising that a wound covering article (e.g., a wound dressing)according to the present invention shows an antimicrobial activity, asdemonstrated by release tests of dissolved silver, as well as byefficacy studies. These studies demonstrate a marked antibacterialactivity against Escherichia coli and Pseudomonas aeruginosa and asomewhat lower activity against Staphylococcus aureus and Enterococcushirae, in this order.

A composite according to the present invention is useful, in particular,as a wound dressing or wound covering such as a compress. Its use inskin care, e.g., as a cosmetic towelette or in baby care is advantageousas well, particularly, because the antimicrobial metal in elemental formdoes not directly contact the skin.

A composite of the present invention in the form of, e.g., a wounddressing or other wound covering material which comprises anantimicrobial metal such as silver shows many advantages, including thefollowing:

-   -   upon contact of the silver layer with a wound fluid, silver        (ions) is (are) released and exert(s) an antimicrobial effect,    -   there is no direct abrasion or release of silver particles into        the wound or onto the skin, which minimizes the risk of        complications in wound healing or skin care,    -   where a mesh, perforated film or the like is provided as a cover        layer over a textile material (as liquid-absorbing material)        fibers from the textile material are prevented from being        released into the wound and/or adhering to the wound.

Surprisingly, the structure according to the present invention can berealized without, or at least without substantial loss, of antimicrobialactivity. In the case of silver, this activity is observed already witha very slight coating of silver, and a coating of preferably at leastabout 10 mg silver/m² is particularly preferred to ensure satisfactoryantimicrobial activity. More silver can also be applied, e.g., forreasons of the manufacturing process. It has been shown, for example,that the application of as much as about 600 mg/m² of silver does notharm the user.

A comparison with known silver-containing wound dressings has shown thata dressing according to the present invention releases an advantageouslyhigh amount of silver at the beginning of the application. Moreover, therelease rate is also sufficiently high over an extended period afterapplication; excessive doping with silver is, therefore, not required,and the wound dressing does not have to be replaced already after ashort period of time. This is of great advantage to users since they canuse the dressing for longer periods without loss of antimicrobial(disinfecting) activity.

Another advantage of a dressing according to the present invention isrelated to abrasion. Rubbing one's finger on the side of the dressingwhich faces the skin reveals no abraded material, let alone blackdiscoloration, in contrast to known wound dressings. This isparticularly advantageous, in particular, for aesthetic reasons, fordressings that are used without a physician's supervision.

In addition to its use as a dressing or wound covering in the form of,e.g., a compress, the composite according to the present invention canalso be used in other areas, e.g., for skin care applications. Forexample, moistened skin may be covered or wiped with the composite, forexample in the form of a cloth. The moisture will penetrate the coverlayer into the moisture-absorbing layer and thereby contact the metal(silver) layer. The antimicrobial metal will be released, therebyproviding the antimicrobial effect associated with the metal. One of theadvantages of the composite of the present invention is that the skinwill not get discolored in these cosmetic uses. This is a substantialimprovement over conventionally used products such as, e.g., baby carewipes and dressings.

Other exemplary embodiments and advantages of the present invention maybe ascertained by reviewing the present disclosure and the accompanyingdrawing.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is further described in the detailed descriptionwhich follows, in reference to the noted plurality of drawings by way ofnon-limiting examples of exemplary embodiments of the present invention,in which like reference numerals represent similar parts throughout theseveral views of the drawings, and wherein:

FIG. 1 shows the results of discoloration tests carried out with variouswound dressings;

FIG. 2 shows top and cross-sectional schematic views of the generalstructure of an embodiment of the present invention;

FIG. 3 shows a top schematic view of an embodiment of the presentinvention in the form of a bandage product; and

FIG. 4 shows a cross-sectional schematic view of an embodiment of thepresent invention in the form of a bandage product.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The particulars shown herein are by way of example and for purposes ofillustrative discussion of the embodiments of the present invention onlyand are presented in the cause of providing what is believed to be themost useful and readily understood description of the principles andconceptual aspects of the present invention. In this regard, no attemptis made to show structural details of the present invention in moredetail than is necessary for the fundamental understanding of thepresent invention, the description taken with the drawings makingapparent to those skilled in the art how the several forms of thepresent invention may be embodied in practice.

Abrasion resistance tests were used to examine abrasion resistance.These tests were analogous to the rubbing fastness test for dyes andprints according to DIN 54021. The subsequent evaluation was carried outaccording to ISO 105-A03: 1993 with a gray scale of from 1 to 5. 1represents a strong, black discoloration, and 5 represents nodiscoloration at all. The results are shown in FIG. 1, wherein thetested products are identified as follows:

-   -   A: Acticoat®; grayness: 3    -   B: silver-coated dressing, silver facing the skin; grayness: 2    -   C: dressing according to the invention, manufactured as        described below; grayness: 5

The dressing according to the present invention (FIG. 1, C) has agrayness of 5, i.e., shows no discoloration. The comparative products,on the other hand, show discolorations with a grayness of 2 to 3. Thisadvantageous reduction of abrasion in the case of the product of theinvention is advantageous, especially, for aesthetic reasons.

FIG. 2 shows top and cross-sectional schematic views of the generalstructure of an embodiment of the composite according to the presentinvention. A liquid-permeable layer (2) is laminated onto aliquid-absorbing layer (1). On the side which faces layer (1), layer (2)is coated with silver (3). In a preferred embodiment, a layer ofaluminum (4) is arranged between layer (1) and the silver coating (3).The aluminum layer makes it easier to coat the silver more uniformly andimproves the appearance.

The composite according to the present invention is particularlysuitable for use in, or as a wound dressing for self-adhesive bandageproducts, and also as an isolated wound covering that may beadditionally fastened to the wound.

FIGS. 3 and 4 show top and cross-sectional schematic views of anotherembodiment of a material according to the present invention in the formof an adhesive strip. The dressing (A) which comprises the followinglayers:

-   -   liquid-absorbing layer (1)    -   liquid-permeable layer (2)    -   aluminum layer (4)    -   silver layer (3)        is provided on a backing layer (5) which is coated with an        adhesive layer (6). The strip thus has a structure which is        similar to that of classic bandages. Prior to use, the adhesive        layer and the wound covering may be covered with a sealing paper        (7).

Where additional adhesion is desired, the dressing according to theinvention can be adhered to the skin by adding adhesive around the edgeas shown in FIG. 3. In this case, the dressing according to the presentinvention will have a structure similar to that of known wound bandages.Peripheral adhesion is possible as in the case of bandages, as isadhesion on both sides as in the case of rolled stock.

The dressing material according to the present invention—with or withoutadditional edge adhesive—may be placed on a wound in the usual way, withsubstantially no elemental silver coming into contact with the wound.

Once the silver-containing dressing is removed, the antibacterial effectceases. Usually, the skin or wound will not have to be washed as noantiseptics and antibiotics will have to be removed.

EXAMPLE

A commercially available polyethylene net (Delnet®, available fromApplied Extrusion Technologies, and also available from Smith & NephewExtruded Films Ltd. U.K.), having triangle-shaped holes (length oflongest bisector: 400-700 μm) is coated, by vapor deposition, first withaluminum and then with silver (alternatively, a commercially availablePE net that already is coated with aluminum may be used). The areaweight of the resultant Al and Ag coated net is about 20 g/m². Thecontent of Al is about 60-80 mg/m² and the content of Ag is about 60-460mg/m². The coated net is laminated to a needle-punched nonwoven(Malivlies) with the coated side facing the nonwoven. The nonwoven iscomposed of about 75 weight-% of rayon (viscose) and about 25 weight-%of polyethylene/polypropylene fibers and has an area weight of about 120g/m². Lamination is carried out under heat and pressure (by slightlymelting the PE/PP fibers and pressing the two layers together).

A material which was made as described above showed the followingproperties:

-   Area weight (DIN EN 29073-1): 125 g/m²-   Thickness (DIN EN 29073-2): 0.75 mm-   Maximum tensile strength (DIN EN 29073-3): 15.8 N/cm-   Delamination/peeling strength (DIN 53357): 0.95 N/cm-   Minimum single value of delamination/peeling strength (DIN 53357):    0.40 N/cm-   Liquid absorption (DIN 53923): 620 g/m²-   Release of silver (see the method described below): 0.46 mg/l after    24 h-   Efficacy: The antimicrobial activity against Staphylococcus aureus,    Enterococcus hirae, Escherichia coli, Pseudomonas aeruginosa and    Candida albicans was tested. It was found that in all cases the    material showed bactericidal, bacteriostatic and/or fungicidal    activity.    Method of Determining Release of Silver:

The release of silver was determined by an extraction of the silver froma sample of the material (square with a side of 30±1 cm) into aphosphate-buffered saline solution (15 ml of PBS solution) at 31° C. for24 h. The PBS solution is described by Dulbecco (John Paul, “Zell- undGewebekulturen”, Walter de Gruyter Publishers, 1980, p. 92). The contentof Ca and Mg ions was adjusted to wound fluid levels (0.19 g/L ofCaCl₂×2 H2O; 0.27 g/L of MgSO₄×7 H2O; Geigy Scientific Tables, Vol. 3,Ciba-Geigy Ltd., 8th Ed. 1984, p 82). Following the extraction, thesample was carefully removed from the solution. The aqueous phase wasacidified and the silver concentration was determined by atomicabsorption spectroscopy using an air/C₂H₂ flame at a wavelength of 328.1nm.

It is noted that the foregoing examples have been provided merely forthe purpose of explanation and are in no way to be construed as limitingof the present invention. While the present invention has been describedwith reference to an exemplary embodiment, it is understood that thewords which have been used herein are words of description andillustration, rather than words of limitation. Changes may be made,within the purview of the appended claims, as presently stated and asamended, without departing from the scope and spirit of the presentinvention in its aspects. Although the present invention has beendescribed herein with reference to particular means, materials andembodiments, the present invention is not intended to be limited to theparticulars disclosed herein; rather, the present invention extends toall functionally equivalent structures, methods and uses, such as arewithin the scope of the appended claims.

1. An antimicrobial composite comprising a first, liquid-permeable layerand a second layer arranged on the first layer, wherein an antimicrobialmetal in elemental form is present between the first and second layersand substantially no antimicrobial metal in elemental form is present onexterior surfaces of the composite.
 2. The composite of claim 1, whereinthe first layer comprises at least one of a perforated film and a mesh.3. The composite of claim 2, wherein the first layer comprises apolyethylene mesh.
 4. The composite of claim 3, wherein the polyethylenemesh comprises openings having a size of from about 400 μm to about 700μm.
 5. The composite of claim 1, wherein the first layer has a thicknessof from about 0.05 mm to about 0.5 mm.
 6. The composite of claim 1,wherein the second layer is one of a liquid-permeable layer and aliquid-absorbing layer.
 7. The composite of claim 6, wherein the secondlayer has a thickness of from about 0.02 mm to about 2.5 mm.
 8. Thecomposite of claim 7, wherein the second layer comprises asuperabsorber.
 9. The composite of claim 1, wherein the antimicrobialmetal comprises Ag and alloys thereof.
 10. The composite of claim 9,wherein the antimicrobial metal is present in an amount of from about 1mg/m² to about 1 g/m².
 11. The composite of claim 1, wherein the firstlayer has a silver coating on a surface thereof which faces the secondlayer.
 12. The composite of claim 9, wherein the composite shows a24-hour release of the silver of from about 0.1 mg/m² to about 2 mg/m².13. A wound covering article comprising the composite of claim
 1. 14. Awound covering article comprising an antimicrobial composite whichcomprises a first, liquid-permeable layer and a second layer over thefirst layer, wherein an antimicrobial metal in elemental form is presentbetween the first and second layers, the article further comprising abacking material arranged on the second layer.
 15. The article of claim14, which is one of a wound dressing, a compress, and a bandage.
 16. Anantimicrobial skin care article which comprises the composite ofclaim
 1. 17. A method of covering a wound, wherein the method comprisesplacing the wound covering article of claim 14 on the wound so that thefirst layer of the composite contacts the wound.
 18. A process of makingan antimicrobial composite, the process comprising bonding together afirst, liquid-permeable material and a second material which is at leastone of liquid-permeable and liquid-absorbing, wherein at least one ofthe first and second materials is coated with an antimicrobial metal inelemental form on a surface thereof which faces the other material, andwherein substantially no antimicrobial metal in elemental form ispresent on an exterior surface of the resultant composite.
 19. Theprocess of claim 18, wherein the process comprises providing aliquid-permeable, sheet-like material, coating one side of the materialwith an antimicrobial metal in elemental form and bonding aliquid-absorbing material to a side of the liquid-permeable materialwhich has the antimicrobial metal thereon.
 20. The process of claim 18,wherein the liquid-permeable material is coated with the metal by atechnique which comprises vapor deposition.